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Metabolomic adaptations and correlates of survival to immune checkpoint blockade

Author

Listed:
  • Haoxin Li

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Harvard University)

  • Kevin Bullock

    (Broad Institute of MIT and Harvard)

  • Carino Gurjao

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • David Braun

    (Dana-Farber Cancer Institute)

  • Sachet A. Shukla

    (Dana-Farber Cancer Institute)

  • Dominick Bossé

    (Dana-Farber Cancer Institute)

  • Aly-Khan A. Lalani

    (Dana-Farber Cancer Institute)

  • Shuba Gopal

    (Broad Institute of MIT and Harvard)

  • Chelsea Jin

    (Bristol-Myers Squibb)

  • Christine Horak

    (Bristol-Myers Squibb)

  • Megan Wind-Rotolo

    (Bristol-Myers Squibb)

  • Sabina Signoretti

    (Dana-Farber Cancer Institute)

  • David F. McDermott

    (Beth Israel Deaconess Medical Center)

  • Gordon J. Freeman

    (Dana-Farber Cancer Institute)

  • Eliezer M. Allen

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital, Harvard Medical School)

  • Stuart L. Schreiber

    (Broad Institute of MIT and Harvard
    Harvard University)

  • F. Stephen Hodi

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital, Harvard Medical School)

  • William R. Sellers

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Levi A. Garraway

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital, Harvard Medical School)

  • Clary B. Clish

    (Broad Institute of MIT and Harvard)

  • Toni K. Choueiri

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital, Harvard Medical School)

  • Marios Giannakis

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital, Harvard Medical School)

Abstract

Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase (IDO/TDO) inhibitors.

Suggested Citation

  • Haoxin Li & Kevin Bullock & Carino Gurjao & David Braun & Sachet A. Shukla & Dominick Bossé & Aly-Khan A. Lalani & Shuba Gopal & Chelsea Jin & Christine Horak & Megan Wind-Rotolo & Sabina Signoretti &, 2019. "Metabolomic adaptations and correlates of survival to immune checkpoint blockade," Nature Communications, Nature, vol. 10(1), pages 1-6, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12361-9
    DOI: 10.1038/s41467-019-12361-9
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    Cited by:

    1. Lei Zhang & Li Jiang & Liang Yu & Qin Li & Xiangjun Tian & Jingquan He & Ling Zeng & Yuqin Yang & Chaoran Wang & Yuhan Wei & Xiaoyue Jiang & Jing Li & Xiaolu Ge & Qisheng Gu & Jikun Li & Di Wu & Antho, 2022. "Inhibition of UBA6 by inosine augments tumour immunogenicity and responses," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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